Loss of heterozygosity at the thymidylate synthase (TS) locus on chromosome 18 affects tumor response and survival in individuals heterozygous for a 28-bp polymorphism in the TS gene.
Single nucleotide polymorphism in the 5' tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients.
In this study, we investigated the association between both DPD and TS expressions in primary colorectal tumor and the antitumor effect in patients with metastatic colorectal cancer when treated with a fluoropyrimidine-based protocol.
DPD and TS expressions were measured by reverse transcription-PCR in surgically resected materials of primary colorectal tumors from 37 patients who went on to receive oral treatment of uracil and tegafur and leucovorin for either synchronous or metachronous metastatic diseases.
Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression levels: predictors for survival in colorectal cancer patients receiving adjuvant 5-fluorouracil.
Studies thus far involving colorectal tumors obtained from patients have focused predominantly on the predictive value of levels of TS expression and p53 mutations in determining response to 5-FU.
Mutations were detected at positions 961 and/or 1031 in the 3'-untranslated regions of the TS gene from the metastases; mutations at these sites were also detected in DNA isolated from normal colon mucosa (n=4) and primary colorectal tumors (n=4).
This trial demonstrated that intratumoral TS/beta-actin messenger RNA (mRNA) ratio can accurately predict which metastatic colorectal tumors will be resistant to a leucovorin-modulated 5-FU infusion and which have a high likelihood of responding to such a regimen.